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  • Academic
    dfatibal@stanford.edu
    University - Scholar Department: School of Medicine Position: Medical Fellow

Additional Info

  • Mail Code: 5151

All Publications

  • A big step for MYC-targeted therapies. Trends in cancer Atibalentja, D. F., Deutzmann, A., Felsher, D. W. 2024

    Abstract

    The MYC proto-oncogene encodes a master transcriptional regulator that is frequently dysregulated in human cancer. Decades of efforts have failed to identify a MYC-targeted therapeutic, and this is still considered to be a holy grail in drug development. We highlight a recent report by Garralda et al. of a Phase 1 clinical trial of OMO-103 in patients with solid malignancies.

    View details for DOI 10.1016/j.trecan.2024.03.009

    View details for PubMedID 38580534

  • Anti-PD-L1 F(ab) Conjugated PEG-PLGA Nanoparticle Enhances Immune Checkpoint Therapy. Nanotheranostics Lee, C. K., Atibalentja, D. F., Yao, L. E., Park, J., Kuruvilla, S., Felsher, D. W. 2022; 6 (3): 243-255

    Abstract

    Background: Immune checkpoint therapies are effective in the treatment of a subset of patients in many different cancers. Immunotherapy offers limited efficacy in part because of rapid drug clearance and off-target associated toxicity. PEG-PLGA is a FDA approved, safe, biodegradable polymer with flexible size control. The delivery of immune checkpoint inhibitors such as anti-PD-L1 (α-PD-L1) via PEG-PLGA polymer has the potential to increase bioavailability and reduce immune clearance to enhance clinical efficacy and reduce toxicity. Methods: The Fc truncated F(ab) portion of α-PD-L1 monoclonal antibody (α-PD-L1 mAb) was attached to a PEG-PLGA polymer. α-PD-L1 F(ab)-PEG-PLGA polymers were incubated in oil-in-water emulsion to form a α-PD-L1 F(ab)-PEG-PLGA nanoparticle (α-PD-L1 NP). α-PD-L1 NP was characterized for size, polarity, toxicity and stability. The relative efficacy of α-PD-L1 NP to α-PD-L1 mAb was measured when delivered either intraperitoneally (IP) or intravenously (IV) in a subcutaneous mouse colon cancer model (MC38). Antibody retention was measured using fluorescence imaging. Immune profile in mice was examined by flow cytometry and immunohistochemistry. Results: Engineered α-PD-L1 NP was found to have pharmacological properties that are potentially advantageous compared to α-PD-L1 mAb. The surface charge of α-PD-L1 NP was optimal for both tumor cell uptake and reduced self-aggregation. The modified size of α-PD-L1 NP reduced renal excretion and mononuclear phagocyte uptake, which allowed the NP to be retained in the host system longer. α-PD-L1 NP was non-toxic in vitro and in vivo. α-PD-L1 NP comparably suppressed MC38 tumor growth. α-PD-L1 NP appeared to elicit an increased immune response as measured by increase in germinal center area in the spleen and in innate immune cell activation in the tumor. Finally, we observed that generally, for both α-PD-L1 NP and α-PD-L1 mAb, the IP route was more effective than IV route for tumor reduction. Conclusion: α-PD-L1 NP is a non-toxic, biocompatible synthetic polymer that can extend α-PD-L1 antibody circulation and reduce renal clearance while retaining anti-cancer activity and potentially enhancing immune activation.

    View details for DOI 10.7150/ntno.65544

    View details for PubMedID 35145835

    View details for PubMedCentralID PMC8824669

  • Venetoclax monotherapy for cutaneous blastic plasmacytoid dendritic cell neoplasm. Annals of hematology Schwede, M. n., Tan, I. T., Atibalentja, D. F., Dickman, M. M., Rieger, K. E., Mannis, G. N. 2020

    View details for DOI 10.1007/s00277-020-04276-z

    View details for PubMedID 32968828